System and Method for Drug Detection in Exhaled Breath

ABSTRACT

A portable system is disclosed for collecting a sample from exhaled breath of a subject. Drug substance in the exhaled breath are detected or determined. The sample is collected for further analysis using mass-spectroscopy. The system comprises a sampling unit and a housing arranged to hold the sampling unit, the sampling unit is adapted to collect non-volatile and volatile compounds of the at least one drug substance from the exhaled breath from the subject. The housing has at least one inlet for the subject to exhale into the housing to the sampling unit and at least one outlet for the exhaled breath to exit through.

RELATED APPLICATION DATA

This application is a continuation of U.S. Nonprovisional patentapplication Ser. No. 13/394,609, filed on May 29, 2012, whichapplication was a U.S. national phase of PCT Application No.:PCT/EP2010/063266 filed Sep. 9, 2010. These applications claim thebenefit of priority of U.S. Provisional Patent Application Ser. No.61/240,752, filed Sep. 9, 2009, and titled “A System and Method for DrugDetection in Exhaled Breath”. Each of these applications areincorporated by reference herein in their entirety.

FIELD OF THE INVENTION

This disclosure pertains in general to the field of systems and methodsfor collecting a sample from exhaled breath of a subject, and fordetecting the presence or determining the quantitative amount of atleast one drug substance in said exhaled breath. More particularly theinvention relates to such portable systems.

BACKGROUND

It is known that exhaled breath is commonly used in alcohol testing andtoday's technology makes it possible to perform on-site breath testingwith legally defensible results using infrared spectroscopy.

Testing for other illicit drugs of abuse traditionally requires blood orurine samples. Alternatively specimens comprising hair, sweat or oralfluid could be used. Blood sampling is invasive and requires medicallytrained personnel, why test subject often have to be transported to ahospital for sampling. This is time and effort consuming. With long leadtimes the test result will be too old. Urine sampling is consideredintruding on personal integrity. Even other issues related to samplesand specimens taken from a subject to be tested arise. For instance forblood samples, and especially for urine samples are at risk of thesubject exchanging the samples or using clean samples from anothersubject to avoid being discovered with traces of illicit drugs. Thus,there is a need to provide a non-invasive, not-specimen based apparatus,system and/or method for detecting the presence or determining thequantitative amount of at least one drug substance in a subject.

Hence, an improved apparatus, system and/or method for on-site samplingof a subject for drug substances is desired. Such an apparatus, systemand/or method for sampling the subject for illicit drugs of abuse and/ormedical drugs would be desired. The apparatus, system and/or methodshould be efficient, non-bulky, user friendly both for operators and thesubject. It should further be not intruding and not invasive.

SUMMARY OF THE DISCLOSURE

Accordingly, embodiments of the present invention preferably seek tomitigate, alleviate or eliminate one or more deficiencies, disadvantagesor issues in the art, such as the above-identified, singly or in anycombination by providing a system and a method, according to theappended patent claims.

According to one aspect of the invention, a portable system is providedthat is configured to collect a sample from exhaled breath of a subject,and for detecting the presence or determining the quantitative amount ofat least one drug substance in said exhaled breath.

The invented system is adapted to collect the sample for furtheranalysis using mass-spectroscopy. The system comprises a sampling unitand a housing arranged to hold the sampling unit. The sampling unit isadapted to collect non-volatile and volatile organic compounds of the atleast one drug substance from the exhaled breath from the subject. Thehousing comprises at least one inlet for the subject to exhale into thehousing to the sampling unit and at least one outlet for the exhaledbreath to exit through.

The exhaled breath volume is not stored in a volume for analysis of thechemical contents of the entire breath volume. Rather, traces of thedrug substance are attached to a collecting element and then furtheranalyzed from this element. Analysis is not made online of the breathvolume, but of the traces in the collecting element. The collectingelement may be removable from a housing and sent further for theanalysis. Collection of the traces is made quick, a single exhalationmay be sufficient. Less than 10 subsequent exhalations are more thansufficient to obtain reliable results and improve robustness of thesystem. This is far more convenient and quicker than any previous breathsample collection methods.

Compounds exhaled in expired air may originate from blood by a mechanismof producing a gas phase in the alveoli. Alternatively, compounds mayoriginate from other parts of the airways. Non-volatile and volatilecompounds are transferred from the lungs, possibly carried by anaerosol. Here the non-volatile and the volatile compounds are drugsubstances and could be either medical drugs or legal or illegalnarcotic substances. The drug substances are collected on-site using aportable system comprising a sampling unit. The collected samples couldbe sent to a laboratory for further analysis. Alternatively, compacton-site analysis may be performed. The analysis is performed using asuitable analyzing method like spectroscopy or preferablymass-spectroscopy. The sampling unit could either be a suitable elementfor collecting the non-volatile compounds or be a sampling unitcomprising an element that is suitable to collect both non-volatile andvolatile compounds.

Since the system is small and designed to be easy to handle it can beused by any personnel on-site. Thus the system is adapted to be usedinstead of more intrusive tests like tests based on the much commonurine or blood samples.

The housing could be made of any material like, plastic, metal or glassas long as it is possibly to clean or make the housing aseptic. Thehousing could alternatively or in addition be made of a disposablematerial. In this way the housing may, after being used for sampling,and for some embodiments also as part of the analyze step, be discarded.

Some embodiments of the invention comprise a detachable mouthpieceelement connectable to the inlet and being in communication with saidhousing element.

The detachable mouthpiece could be either a mouthpiece similar to themouthpieces used by alcoholic test or a mask or any other type ofmouthpieces suitable for exhaling through. The mouthpiece could befitted with valves or flow sensors. The valve could be used to separateinspired fro expired air and also serve as a saliva trap. The mouthpiececould be used either for making the inhalation into the portable systemeasier or for sanitation when the system is not a disposable system andtherefore needs to be cleaned between use.

In one embodiment of the portable system the housing is a Solid-phaseextraction (SPE) cartridge or a SPE-column. The housing could also, insome embodiments be a modified type of sorbent tube to make it suitablyto exhale through.

The SPE-cartridge or SPE-column could be used as a housing comprisingthe sampling element or as part of or a sampling unit covered by ahousing. The SPE-cartridge could, after being used for sampling exhaledbreath, be directly placed on a manifold for extracting the drugsubstances from the SPE-cartridge. Hence this provides for making theworkflow easier and smoother since the amount of steps during theanalysis will be reduced. The risk for contaminating the sample duringthe handling will therefore be reduced. The sorbent tube could be usedin a similar fashion as SPE-cartridge/column.

To make it easy to exhale through the SPE-cartridge the cartridge couldbe modified with for example larger inlets and outlets. In oneembodiment of the invention the subject exhales directly into theSPE-cartridge/column or the sorbent tube and the whole cartridge orsorbent tube (being a portable system) could be sent to the laboratoryto be analyzed.

In another embodiment of the invention, the portable system couldcomprise a pump arranged downstream the sampling unit.

The pump could be placed after the housing element and before or afterat least one outlet. The pump is arranged for helping the subject topass the exhaled breath through the portable system.

This breathing assistance could benefit and help test subjects that havea low or reduced breathing capacity.

In yet another embodiment of the invention, the portable system has apressure drop through the system not higher than 2 cm water. To be ableto collect exhaled breath samples from most subjects the pressure dropthrough the system has to be as low as possible. 2 cm water is what aperson diagnosed with Chronic obstructive pulmonary disease (COPD) canbreath through.

In some embodiments of the invention, the sampling unit comprises atleast one filter membrane. The filter membrane has preferably a meshsize to collect particles from the exhaled breath with a size of 0.2-0.7μm. And even more preferably is the filter membrane chosen such that apressure drop of less than 2 cm water occurs between said inlet andoutlet at an exhalation flow rate of over 0 and up to 9 liters persecond.

The flow rate of a subject's exhalation depends on some parameters forexample the subject's age, mental state (MR, Alzheimer's), medicalcondition (sepsis, Parkinson's) or other medications likebenzodiazepines, opiates, neuroleptics, local anesthetics or intoxicantsetc.

The filter membrane could, after the subject has exhaled through thesystem, easily be removed and sent to a laboratory to be analyzed. Theportable system could then be cleaned and a new filter could be put inplace. The filter membrane could also be directly placed inside theaforementioned SPE-cartridge that is either used as a housing or as partof or a sampling unit inside a housing.

In embodiments of the invention the collected particles from the filterare analyzable by mass-spectroscopy.

The mass-spectroscopy is the preferred method, also for otherembodiments than those comprising a filter in the sampling unit, sincethe technology has a very high selectivity and sensibility ofbioanalysis especially with regards to trace analytes in biologicalsamples. The preferable interface is liquid chromatography.

In another embodiment of the invention, is the filter membrane anelectrostatic filter membrane.

An electrostatic filter is here defined as a filter that has anelectrostatic charge that has a polarity opposite the particles thatshould be collected from the exhaled breath.

The filter could be made highly selective to certain drug substances.

In a further embodiment of the invention is the filters emptied fromcollected particles and analyzed by dissolving the collected particlesfrom the exhaled breath in a solvent and placing the solution on aSurface Enhanced Raman Spectroscopy (SERS)-substrate to be analyzedusing Raman spectroscopy. The analysis could also be performed using aSERS-sensor such as a SERS-probe.

In one embodiment of the invention is the at least one filter membraneat least two filter membranes to discriminate at least two differentdrug substances. This is provided by having filter membranes withdifferent filter selectivity.

This may be provided by stacking or arranging at least two filtersadjacent each other. Each filter may have different mesh types orelectrostatic charges. The sampling unit could thus discriminate betweenat least two different drug substances. This could improve the analysis.

In an embodiment, the sampling unit comprises at least one solid-phasemicroextraction (SPME)-cartridge to be further analyzed using gaschromatography-mass spectroscopy GC-MS.

The SPME-cartridge is a hollow fiber that is arranged such that it willtrap the exhaled drug substances. The SPME-cartridge could then beanalyzed directly using GC-MS.

In some embodiments of the invention the portable system comprises acompartment for collecting saliva and/or condensate. The compartmentcould be arranged between the at least one inlet and the sampling unitand/or after the sampling unit and the at least one outlet. This mayprevent clogging of the sampling unit, e.g. when having hydrophobicfilters that may become saturated by condensed humidity or saliva fromthe exhaled breaths.

By arranging the sampling unit inside the housing so that the housingbecomes divided, two spaces could be formed: one space between the atleast one inlet and the sampling unit and one space between the samplingunit and the at least one outlet. By arranging a compartmentcommunicating to the space between the at least one inlet and thesampling unit saliva and/or condensate formed, from the moist in theexhaled breath, on the walls of the housing and on the sampling unit canbe collected. A similar compartment capable to collect condensate couldbe arrange communicating with the space after the sampling unit and theat least on outlet.

This could help to avoid the sampling unit to be saturated due tobecoming wet by saliva, moist and/or condensate.

The compositions of the exhaled particles are believed to reflect theairway liquid fluid, which probably reflects the blood content of thedrug. The drug substances are believed by the inventors to most likelyto come from the central part of the airway system. The non-volatiledrug substances are carried as liquid droplets (aerosol) that are formedduring normal breathing by the turbulent airflow causing theairway-lining fluid to nebulize. The aerosols are possible to collect asexhaled breath condensates. The theory comes from Anesthetic studiesthat have showed that Anesthetic potency correlates with lipidsolubility. Holds true across species and implies when a specifichydrophobic region is occupied the more soluble the anesthetic agent isin blood the faster the drug goes into the body. The drug substancescould also be volatile as part of the exhaled breath.

In an embodiment of the invention, is the detectable drug substanceincluding in the noncomprehensive list comprising Amphetamines, ecstasy,Cannabis (THC and cannabinoids), Opiates heroin/morphine, 6-AM),Cocaine, Benzodiazepines, Propoxyphene, Methadone, Buprenorphine,Tramadol, LSD, Designer/Internet drugs, Kathinon, GHB, Meprobamat,Z-drugs, Tryptamines, Anabolic steroids, Alcohol/markers but are notlimited to these since other illicit drugs not included in the listcould should also be detectable due to similar interchanges with thehuman body as the above mentioned illicit drug substances.

According to another aspect of the invention, a method is provided, forportably collecting a sample from exhaled breath of a subject, and fordetecting the presence or determining the quantitative amount of atleast one drug substance in the exhaled breath. The method comprisescollecting the sample using a system, according to the aforementionedaspect of the invention, from the subject; and analyzing the collectednon-volatile and volatile compounds of the at least one drug substanceusing mass-spectroscopy.

In another embodiment of the method the collecting comprises collectingnon-volatile and volatile compounds of the at least one drug substancefrom the exhaled breath from the subject in a sampling unit held in ahousing of the system.

In another embodiment of the method, the collecting comprising thesubject exhaling into at least one inlet of the housing to the samplingunit and further to at least one outlet to exit from the housing.

In another embodiment, the method comprises discriminating between atleast two different drug substances by means of at least two samplingelements.

The sampling element is defined as an element for suitably collectingthe drug substances. This could either be the sampling unit itself or acollecting element, such as a filter or fiber probe tip, arranged in thesampling unit.

In an embodiment, the method comprises collecting the at least one drugsubstance using at least one filter membrane arranged in the samplingunit.

In an embodiment, the method comprises collecting the at least one drugsubstance using at least one SPME-cartridge arranged in said samplingunit.

Further embodiments of the invention are defined in the dependentclaims, wherein features for the second and subsequent aspects of theinvention are as for the first aspect mutatis mutandis.

It should be emphasized that the term “comprises/comprising” when usedin this specification is taken to specify the presence of statedfeatures, integers, steps or components but does not preclude thepresence or addition of one or more other features, integers, steps,components or groups thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating the invention, the drawings show aspectsof one or more embodiments of the invention. However, it should beunderstood that the present invention is not limited to the precisearrangements and instrumentalities shown in the drawings, wherein:

These and other aspects, features and advantages of which embodiments ofthe invention are capable of will be apparent and elucidated from thefollowing description of embodiments of the present invention, referencebeing made to the accompanying drawings, in which

FIG. 1 is a schematic illustration that shows an embodiment of aportable system configured to collect a sample from exhaled breath of asubject;

FIG. 2a-c is an embodiment showing a housing with the sampling unitcomprising collecting element being a filter membrane;

FIG. 2d is an embodiment showing a housing with a sampling unit being acollecting element being a filter membrane;

FIG. 2e is an embodiment showing a housing with a SPE-cartridge as partof a sampling unit;

FIG. 3a is a schematic illustration that shows an embodiment of aportable system configured to collect a sample from exhaled breath of asubject wherein the sampling unit and the collecting element is aSPME-cartridge;

FIG. 3b is an embodiment showing a portable system configured to collecta sample from exhaled breath of a subject wherein the sampling unit andcollecting element comprises a SPME-cartridge;

FIG. 4 is a graph that shows the pressure drop as a function of thegas-flow using the diameter of the filter as the parameter.

FIG. 5 is a schematic illustration illustrating an embodiment of aportable system configured to collect a sample from exhaled breath of asubject;

FIG. 6 is a flow-chart illustrating a method for using a portable systemconfigured to collect a sample from exhaled breath of a subject;

FIG. 7 shows a chromatogram indicating the presence of amphetamine andmethamphetamine in exhaled breath.

DETAILED DESCRIPTION

Specific embodiments of the invention will now be described withreference to the accompanying drawings. This invention may, however, beembodied in many different forms and should not be construed as limitedto the embodiments set forth herein; rather, these embodiments areprovided so that this disclosure will be thorough and complete, and willfully convey the scope of the invention to those skilled in the art. Theterminology used in the detailed description of the embodimentsillustrated in the accompanying drawings is not intended to be limitingof the invention. In the drawings, like numbers refer to like elements.

In an embodiment of the invention according to FIG. 1 a portablesampling system 10 is shown. The system comprises a housing 12 forholding the sampling unit 14. The housing 12 could either be one soleelement or be constructed out of two or more parts. The housing could bemade of any material or combinations thereof such as, metal, plastic,glass or ceramics.

The housing 12 comprises at least one inlet 15 that is designed to allowa subject to exhale in. The inlet is in one embodiment dimensioned tofit an optional mouth piece 11 preferably of the same size or type as aconventional mouth piece used for alcohol-test. The mouth piece 11prevents contamination between subjects to sample.

The exhaled breath will then enter a first chamber of the housing thatis designed to spread or focus the exhaled breath over or onto thesampling unit 14. The exhaled gas is thus conveyed in the housing 12 tothe sampling unit 14 and brought into contact with the sampling unit 14.

The sampling unit comprises an arrangement that holds an element 13 forcollecting at least one drug substance being non-volatile or volatilecompounds from the volume of exhaled breath conveyed in the flow in thehousing 12. It should be noted that the sampling unit 14 is not to beconfused with an electronic sampling unit. The collecting element 13 isa physical entity on which the drug substance is collected. Collectionmay in different embodiments be based on various principles, singly orin combination, comprising depositing, catching, fastening, condensingof non-volatile and/or volatile constituents on the collecting element13.

The element for collecting 13 the at least one drug substance is in someembodiments a filter membrane. Alternatively, or in addition, thecollecting element 13 comprises an improved Solid phase micro-extraction(SPME)-cartridge. Alternatively, or in addition, the collecting element13 comprises silica, polymers, imprinted polymers, or molecule imprintedpolymers.

The selectivity of the collection element 13 can be controlled by theuse of different types of collecting elements 13. When using silica (forexample C4, C8 (hydrophilic) or C18 (hydrophobic) etc) either as amembrane, beads or gel, the selectivity depends on how hydrophobic thedrug substances are. For polymers the collecting element is preferablyhighly crosslinked porous beads. These could be used to separatemolecules depending on the size of the particle being filtered throughthe beads or how they bond with the surface of the polymers. Theimprinted polymers such as molecular imprinted polymers are highlyselective to a specific molecule or group of molecules with a size andshape being the same or similar to the cavities of the molecularimprinting. The cavities are made using a template and work as aselective binding sites.

The at least one drug substance may comprise one or more drug compounds.

To allow for a low pressure drop through the system 10 the outlet 16 is,in one embodiment of the invention, the whole back of the housing 12,which is the opening of the outlet 16. The filter is in this embodimentfor instance attached to the housing 12 with retaining elements, such asclips. The filter may also be attached to the housing 12 by means of asecond housing element, which may be a ring formed element that iseither screwed or slid onto the first housing element retaining thefilter. The filter itself will then form the back outlet opening 16 ofthe housing 12 while it is removable kept in the housing 12 by theretainer means.

In an embodiment, the second housing element, that is either screwed orslid onto the first housing element, comprises one central outlet 16.Alternatively, or in addition, many outlets 16 are arranged over thesurface of the second outlet 16 in such a manner that the pressure dropis as low as possible when exhaling breath through the system 10.

In yet another embodiment the sampling unit 14 comprising the elementsuitably for collecting the drug substances 13 is hold in place by ormade of spacer pieces attached to the walls of the housing 12 and eitherthe sampling unit 14 or direct onto the element suitably for collectingthe drug substances 13. Thus passages are created that will allow for asubject to easily exhale breath trough the portable sampling system 10.

In one embodiment, the sampling unit 14 is arranged such that there isan air passage around it so that the air can still flow through thesampling unit 14 even if the comprised filter (collecting element 13)became saturated causing an undesired high pressure drop. This kind ofsampling unit 14 arrangement thus further improves the exhaled breathspreading inside the housing 12, whereby the surface of the samplingunit 12 is used more optimal.

In some embodiments the system 10 comprises a pump 17, arrangeddownstream the sampling unit 14, after the housing 12 and before orafter at least one outlet 16 of the housing 12. The pump 17 is adaptedto assists the subject to pass the exhaled breath through said system10. The pump 17 generates a negative pressure over the sampling unit 14.For example if the subject has reduced lung capacity due to drug abuseor illness, this is advantageous. The sampling is assisted by the flowthrough the sampling unit 14 generated by the pump 17.

In some embodiments a flow sensor is arranged downstream the inlet 15.The sensor could be arranged for measuring an exhaled volume or flow ofexhaled breath. The sensor may be a differential pressure sensor formeasuring the differential pressure across the sampling unit 14. Theoutput from the differential pressure sensor is in non-turbulent flowlinear to the flow through the sampling unit 14 with could be used tocalculate the volume of exhaled breath having passed the sampling unit14. This could then be used for calculation of the concentration of drugsubstances in the exhaled breath. Alternatively, or in addition, thevolume data may be used for determining if sufficient volume has reachedthe sampling unit 14 for reliably determining the presence or thequantitative amount of a drug substance in the exhaled breath.

Some embodiments of the system 10 comprises at least one compartment forcollecting saliva and/or condensate. The compartment could be arrangedeither between said at least one inlet 15 and said sampling unit 14and/or after said sampling unit 14 and said at least one outlet 16. Thiswould allow for saliva comprised in the exhaled breath or condensateformed, from the moist in the exhaled breath, on the sampling unit 14 tobe collected and not affect the sampling unit 14 and the comprisedcollecting element 13 in any negative way. Negative ways could here be awet or clogged sampling element 13 that collects the drug substancesi.e. a filter membrane or a SPME-cartridge.

FIG. 2a is an embodiment showing a housing 12 with a outlet 16 and anmouthpiece 11 in flow communication with an inlet. The outlet 16 coversthe main portion of the back of the housing 12. In FIG. 2b can thesampling unit 14 comprising a collecting element 13, being a filtermembrane, be seen through the outlet 16. FIG. 2c shows the main parts ofthis embodiment of the portable system 10; a first housing part 12 a; asecond housing part 12 b; a sampling unit 14 comprising a filtermembrane. The housing 12 is made of two parts the first part 12 acomprises an inlet 15 that can be in flow communication with amouthpiece 11 and a second part 12 b with one large outlet 16.

FIG. 2d is an alternative or additional embodiment showing a housing 12comprising a sampling unit being a filter membrane. This embodimentcomprises two parts that when attached forms a housing 12 that holds afilter membrane. The housing comprises an inlet 15 suitable for amouthpiece 11 and an outlet 16. This embodiment is very small, lightweighted and easy to carry.

FIG. 2e is a further embodiment showing a housing comprising two part 12a, 12 b with a SPE-cartridge 21 as part of a sampling unit 14. TheSPE-cartridge 21 comprising either silica beads, polymers or imprintedpolymers for collecting the drug substance but could alternatively befitted with a filter membrane. The SPE-cartridge 21 is seen sticking outthrough a outlet of the second part of the housing 12 b and the bottomof the SPE-cartridge 22 works as the systems outlet for the exhaledbreath. In a further embodiment of a similar portable system the housingis a modified SPE-cartridge. This means that the system can be madesmaller than the system showed in FIG. 2e . After use, in both of theabove cases, the whole SPE-cartridge 21 can be sealed and then sent to alaboratory where it could be directly placed on a manifold which willhelp to reduce the handling of the samples and at the same time reducethe possibilities of the sample to be contaminated.

FIG. 3a is a schematic illustration that shows an embodiment of aportable system 30 configured to collect a sample from exhaled breath ofa subject through an inlet 31 in flow communication with a housing 32.Wherein the sampling unit is a SPME-cartridge holder 34 and thecollecting element is a SPME-cartridge 33. FIG. 3b shows a furtherembodiment of the portable system 30 configured to collect a sample fromexhaled breath of a subject by means of a SPME-cartridge 33.

The system comprises a housing made of two part 32 a and 32 b. The firsthousing part 32 a comprises with an inlet 31 in flow connection with adetachable mouthpiece 11. The housing comprises an outlet through whichthe SPME-cartridge holder 34 can be observed. In FIG. 3b theSPME-cartridge and the housing is shown as separate items.

Another embodiment, working similar to the described SPE-cartridgeembodiment, is an embodiment wherein the sampling unit comprises asorbent tube as the collecting element or wherein the sorbent tube isthe sampling unit. Alternatively the sorbet unit, as for theSPE-cartridge case, could be the housing.

In the embodiments of the system 10 wherein a collecting element 13 isin form of a filter, the filter comprises a filtering membrane for theexhaled breath to diffuse through. The filter membrane is made of asuitable absorbing, yet gas permeable, material. The filter membranewill have a structure that catches and collects the drug substancesbeing, exhaled particles, non-volatile or volatile compounds whileletting gas pass through. Preferably the filter membrane is operable tosample or remove chemical compounds (drug substances) from the air witha high volumetric capacity while maintaining a low pressure drop acrossthe filter substrate.

The filter membrane could also be an electrostatic filter in someembodiments.

The filter membrane may be of a nonwoven polymeric fibrous web that istransformed into an electret. The electret is a dielectric materialexhibiting a quasi-permanent electric charge. Electret filters usuallylose their charge upon long-term use. However, in the presentapplication, the filter will not be used extensive times. A singleexhalation may be sufficient to collect sufficient traces for a reliableanalysis. Therefore, loss of electric charge will not be a concern inimplementations of electret filter embodiments.

The inventors believe that there could be different mechanisms that makeit possible to use the filter membrane to collect the drug substancesthat could be either volatile organic compounds or non-volatile organiccompounds.

The filter membrane is preferable a layered filter membrane but couldalso be a single layer filter membrane.

The filter membrane may also be corrugated to enhance the filtering areawithin a given housing volume.

How the collecting of the analytes work is not entirely investigated.However, applicants believe that the first layer collects droplets byabsorption or particles from exhaled breath. In addition, oralternatively, it could also be from exhaled breath absorbing orcondensates and the small amount of water then evaporates, thus leavingthousands of analytes from the exhaled breath on the first surface. Inaddition, or alternatively, the analytes may be part of an aerosolconveyed by the exhaled breath, which aerosol particles stick to thefirst layer. Evaporation may also take place of aerosol, which thenleaves the traces of the analytes on the first layer for analysis.

The first layer is gas permeable thus the analytes not collected on thefirst layer will pass through entering the second layer being a fiberlike filter made of a synthetic, natural or half synthetic material. Thesecond layer has a fiber density creating a surface volume. The gatewill pass through the second layer that will collect the analytes bysimilar mechanism as described above but it could also be due to chargesof the fibers that will make the analytes stick to the surface of thefibers.

The filter could also have layers of other materials such as silica,polymers, and/or imprinted polymers but could also be other types ofmaterials that could collect analytes from exhaled breath.

In some embodiments, the filter material comprises glass fibers. Theglass fibers may be bearing a permanent electrostatic charge to improvethe efficiency of the filter in the current application. The glassfibers may be randomly oriented. The glass fibers may be held in placeby suitable outer layers of a different material. The glass fibers mayalso be partly melt together to provide a solid filter cartridge. Ahighly efficient filter for collecting traces of chemical compounds fromexhaled breath may thus be provided while maintaining a low pressuredrop at high exhalation rates, as desired.

Due to the short time of usage, there is no risk of clogging the filtersor reaching an increased pressure drop due to filter clogging.

FIG. 4 is a graph 40 that shows the pressure drop in mm water Y as afunction of the gas-flow X in the unit liter per minute and wherein thediameter of the filter is a parameter. The diameters of the filterstested are 10 mm (curve 41), 13 mm (curve 42), 16 mm (curve 43), 19 mm(curve 44) and 22 mm (curve 45).

When analyzing the filters, a small filter volume to extract from ispreferred. This could be done, for this particular filter membrane, bymaking the diameter smaller. But at the same time the volume exhaledthough the filter membrane should not generate a high drop of pressure.Preferably, the filter membrane should collect drug substances from a,as large volume of one deeply exhaled breath, as possible and at thesame time not generate a high pressure drop. A healthy person should beable to handle a pressure drop of about 20 mm of water. According toFIG. 4 a filter size, for this particular filter membrane, of about 16mm should be possible to use and still have an acceptable pressure drop.By modifying the physical or the chemical properties of the filtermembrane or remove layers, smaller diameters may be possible.

The sensitivity of the used LC/MS method and this particular filtermembrane makes it possible to detect drug substances from one exhaledbreath.

Below is a table (table 3) showing results from a pre-study on fivesubjects at three different occasions. Here methadone (Mtd) in exhaledbreath in pictogram per minute of exhalation is measured from the fivesubjects using three different collecting times, one collecting time ateach occasion. All measurements were performed after the subject hadtheir individual dose of methadone delivered to them.

TABLE 3 Methadone dose Mtd pg/min Mtd pg/min Mtd pg/min Case no (mg/d) 1min 3 min 10 min 1 90 200 170 3840 2 120 50 40 27 3 100 10900 233 150 4110 100 167 120 5 100 220 117 90

At the first occasion the subject exhaled for one minute, at the secondoccasion for three minutes and at the third occasion for 10 minutes.Except for subject number two who was not compliant and theexceptionally high values for subject number three and one at one of theoccasions respectively, the results indicates that short collectingtimes are possible and even shorter collecting times should beperformable using this particular filter membrane since the sensitivityof the LC-MS method allows for detections of lower amounts than themeasured. The measured amount of drug substance could also be obtainedby a small filter volume to extract from. This according to whatpreviously have been described.

FIG. 5 is a schematic illustration illustrating an embodiment of aportable system 50 configured to collect a sample from exhaled breath ofa subject 51. The subject will exhale through an optional mouthpiece 52being in flow communication with a housing 54 via at least one inlet 53.The housing comprises a sampling unit 55 that could be either acollecting element or comprises a collecting element for collecting thedrug substances from the exhaled breath. The exhaled breath exits thehousing through at least one outlet 56. The sampling unit 55 and/orcollecting element is sent to a laboratory 57 to be analyzed. In someembodiments of the portable system 50 the housing 54 could be thesampling unit 55.

The sampling unit 55 could comprise more than one collecting element,and/or the housing 54 could comprise more than one sampling unit, in anycombination, suitably for collecting drug substances This will make itpossible to discriminate between different drug substances, thus makingthe analysis easier to perform. For example could the sampling unit 55comprise at least one filter membrane and at least one SPME-cartridge.Another combination could include a stack of filter membranes withdifferent physical and/or chemical properties. But multiple filter couldalso be used by using sampling unit 55 comprising areas fitted withdifferent filter membranes.

The sampling system and elements for collecting drug substances shouldbe kept clean and preferable be aseptic but do not need to be sterile.

FIG. 6 is a flow-chart illustrating a method 60 for using a portablesystem configured to collecting a sample 62 of exhaled breath and fordetecting the presence or determining the quantitative amount 63 of atleast one drug substance in the collected sample. The method comprisesthe steps of: A subject exhaling 61 into the invented portable system; asampling unit will collect a sample 62 comprises drug substances; thecollected sample will be analyzed using mass-spectroscopy 63.

In FIG. 7, chromatograms are shown from the identification ofamphetamine (A) and methamphetamine (B) in exhaled breath from onesubject after intake of “amphetamine”. Y are here representing response(CPS) and X time (min). The conventionally analyzed urine and plasmadata of the same subject taken for comparison reasons suggest possibleintake of methamphetamine with amphetamine. Identification using asampling unit and LC-MS-MS analysis was based on the presence ofcompounds with correct retention time and with correct relativeabundance of two product ions. The identification of detected analyteswas based on a correct relative (to amphetamine-d5) retention time. Twoproduct ions from the protonated molecules were monitored foramphetamine (m/z 136->119, Plot No. 75; 136->91 73) two formethamphetamine (m/z 150->119, Plot No. 76; 150->91, Plot No. 74). Noneof the control subjects without drug intake showed any of these peakswhen analyzed from the implemented sampling unit. Thus, detection ofamphetamine (A) and methamphetamine (B) in exhaled breath samples isreliably demonstrated. Further examples are given below.

With reference to FIG. 6 a flow-scheme is used to illustrate theinvented method. A subject will exhale 61 in and out either for acertain time or for a fixed number of times such as 1 to 10 times into aportable system. When breathing a fixed number of times each exhalecould be set to last for a fixed time. The exhalation could also beperformed until a certain volume of exhaled breath has been obtained. Adeep breath is preferred to reach exhaled breath from deep lying lungportions such as the central or the peripheral lung regions.

The exhaled breath will then be collected 62 by the sampling unitcomprising at least one element suitably for collecting drug substancesbefore it exits the system. The sampling unit will then be removed sothat the at least one element suitably for collecting drug substancescan be analyzed 63 using an appropriate mass-spectroscopy method.Alternatively, for some of the previously described embodiments, thewhole housing could be sent to be analyzed.

In the following further examples of implementations of the inventionand how an analysis may be performed is demonstrated. These originalobservations demonstrate drug testing based on sampling of expired air.

Example 1

Twelve patients reporting recent use of amphetamine (7 male, 5 female,ages 22-51) were recruited from two addiction treatment clinics inStockholm (Beroendecentrum Stockholm). History of drug use was assessedby interview and by using two structured questionnaires, AUDIT (foralcohol) and DUDIT (for illicit drugs). The patients scored a median of2.5 (range 0-34) in the AUDIT and 34.5 (range 12-43) in the DUDITquestionnaires. Recent drug intake was further investigated by analysisof blood plasma and urine samples. The urine and EDTA plasma sampleswere collected following the expired air sampling and stored at −80° C.

As control group eight drug-free healthy volunteers (3 male, 5 female,ages 29-67) were recruited. Compounds in expired air were collected bysuction through an SPE cartridge (30 mg SPEC DAS, Varian, Lake Forest,Calif.). The patients were asked to breath in a face mask (no 1516,Intersurgical Ltd, Berkshire, UK) and a three way coupling was used towithdraw breath air. It was estimated that about half of the expired airwas collected into the SPE cartridge via a 3 m long plastic tubing.Following sampling the SPE cartridge was stored at −80° C. andsubsequently eluted with 2% ammonia (25%) in a mixture of methanol andethyl acetate (20/80) at the time of analysis. The eluate was evaporatedto dryness under nitrogen gas after addition of formic acid (10 μL of10% formic acid in MeOH) and the residue was re-dissolved in 30 μL of0.1% formic acid containing internal standard (5.94 ng amphetamined5).

An aliquot of 3 μL was subjected to analysis by SRM UPLC-MS/MS (WatersQuattro Premiere XE). The chromatographic system was a AQUITY UPLC BEHC18 column, 100 mm×1.0 mm, particle size 1.7 μm, with a gradient systemwith A=0.1% formic acid and B=acetonitrile. The linear gradient startedat 100% A and ended at 70% A after 1.7 min. Thereafter 100% was pumpedfor 0.49 min before returning to 100% A.

Two product ions from the protonated molecules were monitored foramphetamine (m/z 136→119 75; 136→91 73), two for methamphetamine (m/z150→119 76; 150→91 74) and one for amphetamine-d5 (m/z 141→124 71, 72)was done by selected reaction monitoring (SRM) in the positiveelectrospray mode, with 25 ms dwell time for each channel. The sourceblock and desolvation temperatures were set at 150 and 350° C.respectively. Standards for quantification were prepared by using thematrix from blank SPE cartridges. Methods used for plasma and urineanalysis were in routine use in the laboratory and based on LC-MStechniques.

In all 12 studied patients amphetamine and/or methamphetamine weredetected in the expired air sample, which was in accordance withself-reported drug intake. In all cases the self-reported intake wassupported by analysis of blood plasma and urine. The presence andrelative levels of amphetamine and methamphetamine indicated mixed druguse of both compounds, which is in accordance with a recent trend inSweden observed in the clinical urine drug testing. In the 8 healthycontrols no amphetamine or methamphetamine were detected.

Drug identification of detected analytes was based on a correct(relative to amphetamine-d5) retention time (±0.5%) and correct (<±20%)relative ion intensity ratio between the two product ions (FIG. 7).These criteria for identification are in accordance with scientificstandards and are being successfully applied in urine drug testing.Since levels were generally low, background signal resulted in failureto fulfil identification criteria in some of the samples despite thefact that a signal was actually present. The amount of substancecollected from expired air ranged from 0.2 to 103 pg/min for amphetamineand <0.3 to 139 pg/min for methamphetamine, see Table 1. No correlationbetween plasma and expired air levels was evident from the results.However, the sampling technique employed could not be validated forextraction efficiency. The SPE cartridge material is normally used forextraction of analytes from aqueous solutions. It is therefore unknownto what degree the amphetamines are trapped from expired air and thereproducibility of the extraction efficiency, which may have contributedto the variability in detected amounts in the expired air samples. Firmconclusions regarding correlation of expired air with blood levels weretherefore not possible in this example. Using a flow meter as describedabove to determine the analyzed volume would provide an efficacymeasure.

The urine and plasma data indicated that in most cases sampling wasperformed close to intake (<24 h), while in other cases low levels (<−5μg/mL) in urine indicated longer times since intake (Table 1). Analyteswere, however, still detected in the expired air. The relativeproportion of amphetamine and methamphetamine in the expired aircorrelated well with plasma results, which further validates thesefindings.

Example 2

Thirteen patients undergoing methadone maintenance treatment (12 males,1 female, ages 31-58) were recruited from the methadone program inStockholm (Rosenlund, Stockholm). The patients were in steady-state andreceived supervised daily doses of methadone between 70 and 155 mg. Thepatients were subjected to constant control of compliance to treatmentby urine drug testing. As a control group ten drug-free healthyvolunteers (4 males, 6 females, ages 29-66) were recruited.

TABLE 1 Expired Case Self-reported Plasma* Urine* air* no drug use ng/mLμg/mL pg/min 1 Amphetamine, diazepam A = 166 A = 107 A = 0.7 M = 1.9 M =0.69 M < 0.3 2 Amphetamine, diazepam A = 62.4 A = 14 A = 0.2 M = 0.6 M =0.08 M < 0.3 3 Amphetamine A = 282 A = 30 A = 0.5 M = 2.1 M = 0.12 M <0.3 4 Amphetamine, methylphenidate A = 110 A = 62 A = 19 M = 27 M = 5.4M = 1.2 5 Amphetamine, zopiclone A = 52 A = 29 A = 0.4 M = 52 M = 19 M =0.4 6 Amphetamine, flunitrazepam, No sample A = 5.3 A = 103 alprazolam,buprenorphine, morphine, M = 62 M = 139 zopiclone 7 Amphetamine A = 4.3A = 0.94 A < 0.6 M = 3.2 M = 0.40 M = 0.5 8 Amphetamine, diazepam,methadone, No sample A = 20 A < 0.3 heroin M = 119 M = 0.6 9Amphetamine, methylphenidate, No sample A = 6.7 A = 0.4 alprazolam,diazepam M = 0.02 M < 0.3 10 Amphetamine, flunitrazepam, A = 535 A = 229A = 0.7 methadone M = 64 M = 15 M < 0.3 11 Amphetamine, clonazepam, A =504 A = 163 A = 5.3 methadone, cannabis M = 274 M = 51 M = 1.3 12Amphetamine, benzodiazepines, A = 2.0 A = 1.3 A = 1.4 heroin, cannabis M= 0.1 M = 0.01 M = 0.3 *A = amphetamine, M = methamphetamine

Sampling of Exhaled Breath

Compounds present in the exhaled breath were collected for 10 min bysuction through a 47 mm Empore C18 disc (from 3M Inc.) using a membranepump to assist the flow (about 300 mL/min). The subjects were asked tobreathe more deeply than normal into a mouth piece (no. 4091148,Palmenco AB, Stockholm, Sweden) mounted in the sampling device holdingthe Empore disc (FIG. 1). It was estimated that all the exhaled breathwas collected through the filter during the sampling period. Followingsampling the Empore disc was dismantled using a tweezers and stored at−80° C. The sampling device was carefully cleaned between uses, whichtakes about 15 min.

Sample preparation: Following storage the Empore disc was cut into 5mm×5 mm pieces using a scalpel and transferred to a 10 mL glasstest-tube. A volume of 100 μL of 100 ng/mL methadone-d3 was added andmixed using a Vortex mixer, 300_L of 2-propanol was added (to wet thesurface), mixed and finally 5 mL of 20% methanol in ethyl acetate wasadded. This mixture was shaken for one hour in a thermostatic bath at37° C. Thereafter, the test-tube was centrifuged for 15 min at 3000×g at10° C., the supernatant transferred to a new 10 mL glass test-tube, andthe extraction procedure repeated using 1 mL of 20% methanol in ethylacetate. Finally the two supernatants were combined, 10_L of 10% aqueousformic acid added and evaporated to dryness under a stream of nitrogenat a temperature of 40° C. The dry residue was dissolved in 100_L of 50%methanol in ethyl acetate.

Mass spectrometry analysis: An aliquot of 3 μL was subjected to analysisby UPLC-MS/MS (Waters Quattro Premier XE). The chromatographic systemwas a Aquity UPLC BEH C18 column, 100 mm×1.0 mm, particle size 1.7 μm,with a gradient system consisting of A=0.1% formic acid andB=acetonitrile. The mobile phase was 95% A for 1.2 min, followed by alinear gradient from 5% B to 65% B to 3.0 min. The equilibration timebetween injections was 4.0 min (95% A). The flow rate was 0.20 mL/min.Two product ions from the protonated molecules were monitored formethadone (m/z 310→265; 310→105) and one for methadone-d3 (m/z 313→268).This was done by SRM in the positive electrospray mode, with 75 ms dwelltime for each channel. The minimum detectable amount (signal to noise 3)injected on column was about ˜0.2 pg.

Quantification: Standards for quantification were prepared fromfortified blank Empore discs. These were prepared by adding 10, 25, 50,100 and 200 μL (corresponds to 3.0, 7.5, 15, 30 and 60 ng on thesurface) of a solution containing 300 ng/mL of methadone. After dryingthe discs were prepared for analysis as described above. Calibrationcurves were constructed using linear regression analysis, with weightingfactor 1/x.

Method validation: Five replications of the calibration curve wereanalyzed on different occasions. Limit of detection (LOD) and lowerlimit of quantification (LLOQ) was assessed by applying 10 pg ofmethadone onto a blank Empore disc and subject it for analysis.Imprecision and accuracy were estimated by analysis of six replicates ofmethadone applied on blank Empore discs at three levels (3.0, 15, 45ng/disc). Recovery of extracting methadone from the Empore disc wasestimated by comparison with a reference sample prepared directly in thefinal extract solvent. Matrix effects were estimated by extracting blankfilter and filter from healthy volunteer and fortify with methadone inthe final extract. This was compared with a reference sample withoutmatrix. In addition, an infusion experiment was performed whereinjection of a control breath extract was injected while infusingmethadone post-column and compared with injection of mobile phase A. Theinfusion rate was 10 μL/min and the infused methadone solution was 0.5μg/mL in 0.1% formic acid in 50% methanol.

The peak area ratio of methadone to methadone-d3 was linear between 3and 60 ng per sample corresponding to 0.3 and 6.0 ng methadone exhaledin breath per min. The correlation coefficients (r2) of the calibrationcurves were between 0.991 and 0.999 (mean 0.996, n=5).

TABLE 2 Summary of data obtained for methadone sampled in exhaled breathfrom 13 methadone maintenance patients. Sampling Mouth time after washMethadone Case Number of Methadone dose intake prior to excretion no.breaths dose (mg/d) (min) sampling (ng/min) 1 90 41 13 No 1.0 2 100 5944 Yes 0.39 3 100 127 27 No 1.9 4 140 91 10 Yes 5.8 5 80 94 25 Yes 1.2 6155 45 10 Yes 0.87 7 100 42 60 Yes 3.5 8 100 56 13 Yes 1.5 9 120 35>10^(a ) No 1.4 10 70 46 12 Yes 0.90 11 100 66 13 Yes 0.93 12 100 90 18Yes >6.0^(b) 13 120 59  8 Yes 2.6 ^(a)Not noted ^(b)Extrapoled valuefrom 180 ng/disc standard was 78

Summary of data obtained for methadone sampled in exhaled breath from 13methadone maintenance patients.

LOD (signal to noise 3) was estimated to 4 pg/sample (˜0.4 pg inbreath/min) and LLOQ (signal to noise 10) was estimated to 15 pg/sample,while the calibrated measuring range was 3.0-60 ng/sample. Imprecision(coefficient of variation, CV) was estimated within series to 1.6%, 1.9%and 2.0% at levels 3.0, 15, and 45 ng/sample (n=6). The accuracy was104%, 109% and 104%, respectively. The extraction recovery of methadonefrom the Empore disc surface was measured in duplicate using samples atthe 15 ng/sample level and was 96.6% (n=4). Matrix effects wereestimated by addition of methadone (15 ng/sample) to extracts preparedfrom blank Empore discs and from Empore discs used for collection ofexhaled breath from a healthy volunteer. The methadone peak area wascompared with the reference sample containing no matrix. The matrixeffect for blank Empore discs was 109% (SD 9, n=8) and for breath samplediscs 108% (SD 40, n=8).

Application of the method: Methadone was detected in the sampled exhaledbreath from all 13 studied patients, which was in accordance with thedaily observed dose intake of methadone (Table 2). In all cases this wasalso supported by compliance to treatment as controlled by routineanalysis of urine and by supervised dose intake. None of the 10 controlsubjects had detectable levels of methadone (<0.005 ng/min) in theexhaled breath samples. The detection level was set by the contributionof methadone-d3 to the two methadone channels.

Identification of detected methadone was based on a correct relative (tomethadone-d3) retention time (±0.5%) and correct (<±20%) relative ionintensity ratio between the two product ions. The amount of methadonecollected from breath was high enough to produce strong analyticalresponse. This makes the identification secure and methadone wasidentified according to these criteria in samples from all methadonepatients. The amount of methadone ranged >15-fold from 0.39 to >6.0 (78)ng/min. The highest value obtained was outside the measuring range andappeared to be an outlier. Table 2 summarizes the results and collecteddata for the 13 patient samples. No difference in results could beobserved between subjects sampled with or without mouth wash prior tosampling (Table 2). No significant correlation of excretion rate withmethadone dose was observed.

Each subject was breathing at own chosen pace. The number of breathsduring the 10 min sampling time was therefore recorded (Table 2). Table2 also reports the actual sampling time after dose intake. Due topractical reasons this time interval could not be the same for allsubjects but varied between 8 and 60 min.

The Empore discs are commercially available, for instance from 3M Inc.These products are made of bonded silica. They are conventionallyintended for use for the solid phase extraction of liquid analytes,which usually are highly diluted. It was hitherto not known to use suchcollective elements as a filter discs for collecting non-volatile orvolatile compounds of substances in a gas, such as exhaled breath.Present applicants have realized this unexpected potential and aboveexample shows the feasibility of that inventive use. As pressure dropthrough the commercially Empore discs is high, some embodiments areprovided with the aforementioned pump assisted breathing through thediscs. Alternatively, or in addition, the discs may be modified toreduce pressure drop over them. This may be done by pinching holesthrough a portion of the surface of the disc. Alternatively, or inaddition, an Empore disc is hold in place by spacer pieces, as describedabove.

A variety of functional groups, such as octadecyl (C18) and octyl (C8)can be bonded to the silica surface to provide non polar interactions.

Each of these sorbents exhibits unique properties of retention andselectivity. This is based on the fact that drug compounds arelipophilic as such because they can pass the blood-brain barrier. Thesorbents, such as C18, render the silica surface lipophilic. Therefore,these collective elements provide for selectivity for a particularanalyte, such as for a specific drug substance.

The choice of which sorbent is best for a particular method will beinfluenced by the percent recovery of analyte from the sample matrix andthe cleanliness of the resulting chromatography.

The present invention has been described above with reference tospecific embodiments. However, other embodiments than the abovedescribed are equally possible within the scope of the invention.Different method steps than those described above, performing the methodby hardware or software, may be provided within the scope of theinvention. The different features and steps of the invention may becombined in other combinations than those described. The scope of theinvention is only limited by the appended patent claims.

The foregoing has been a detailed description of illustrativeembodiments of the invention. It is noted that in the presentspecification and claims appended hereto, conjunctive language such asis used in the phrases “at least one of X, Y and Z” and “one or more ofX, Y, and Z,” unless specifically stated or indicated otherwise, shallbe taken to mean that each item in the conjunctive list can be presentin any number exclusive of every other item in the list or in any numberin combination with any or all other item(s) in the conjunctive list,each of which may also be present in any number. Applying this generalrule, the conjunctive phrases in the foregoing examples in which theconjunctive list consists of X, Y, and Z shall each encompass: one ormore of X; one or more of Y; one or more of Z; one or more of X and oneor more of Y; one or more of Y and one or more of Z; one or more of Xand one or more of Z; and one or more of X, one or more of Y and one ormore of Z.

Various modifications and additions can be made without departing fromthe spirit and scope of this invention. Features of each of the variousembodiments described above may be combined with features of otherdescribed embodiments as appropriate in order to provide a multiplicityof feature combinations in associated new embodiments. Furthermore,while the foregoing describes a number of separate embodiments, what hasbeen described herein is merely illustrative of the application of theprinciples of the present invention. Additionally, although particularmethods herein may be illustrated and/or described as being performed ina specific order, the ordering is highly variable within ordinary skillto achieve aspects of the present disclosure. Accordingly, thisdescription is meant to be taken only by way of example, and not tootherwise limit the scope of this invention.

Exemplary embodiments have been disclosed above and illustrated in theaccompanying drawings. It will be understood by those skilled in the artthat various changes, omissions and additions may be made to that whichis specifically disclosed herein without departing from the spirit andscope of the present invention.

What is claimed is:
 1. A portable system configured to collect a samplefrom exhaled breath of a subject, and for detecting the presence ordetermining the quantitative amount of at least one drug substance insaid exhaled breath, said system being adapted to collect said samplefor further analysis using mass-spectroscopy, said system comprising: asampling unit and a housing arranged to hold said sampling unit, saidsampling unit is adapted to collect at least one of non-volatile andvolatile compounds of said at least one drug substance from said exhaledbreath from said subject; and wherein said housing comprises at leastone inlet for said subject to exhale into said housing to said samplingunit and at least one outlet for said exhaled breath to exit through. 2.The system according to claim 1, comprising a detachable mouthpieceelement connectable to said inlet in communication with said housingelement.
 3. The system according to claim 1, wherein said housing is aSPE cartridge.
 4. The system according to claim 1, wherein said housingis a sorbent tube.
 5. The system according to claim 1, comprising apump, wherein said pump is arranged downstream said sampling unit. 6.The system according to claim 1, wherein the pressure drop through saidsystem is not higher than 2 cm water.
 7. The system according to claim1, wherein said sampling unit comprises at least one filter membrane. 8.The system according to claim 7, wherein said filter membrane is has amesh size to collect particles from said exhaled breath with a size of0.2-0.7 μm.
 9. The system according to claim 7, wherein said filtermembrane is configured such that a pressure drop of less than 2 cm wateroccurs between said inlet and outlet at a exhalation flow rate of about0-9 litre/min.
 10. The system according to claim 7, wherein saidcollected particles from said filter are analyzable by saidmass-spectroscopy.
 11. The system according to claim 7, wherein saidfilter membrane is a electrostatic filter membrane.
 12. The systemaccording to claim 7, wherein said at least on filter membrane comprisesat least two filter membranes configured to discriminate between atleast two different drug substances.
 13. The system according to claim1, wherein said sampling unit comprises at least one SPME-cartridge tobe further analyzed using GC-MS.
 14. The system according to claim 1,wherein a compartment for collecting at least one of saliva orcondensate is disposed between said at least one inlet and said samplingunit and/or after said sampling unit and said at least one outlet. 15.The system according to claim 1, wherein said at least one ofnon-volatile or volatile compounds of said at least one drug substancein said exhaled breath are compounds that can pass from the subject'sblood via the lung membrane.
 16. The system according to claim 15,wherein said drug substance comprises at least one of Amphetamine,ecstasy, Cannabis, THC and cannabinoids, Opiates, heroin, morphine,6-AM, Cocaine, Benzodiazepines, Propoxyphene, Methadone, Buprenorphine,Tramadol, LSD, Designer/Internet drugs, Kathinon, GHB, Meprobamat,Z-drugs, Tryptamines, Anabolic steroids, Alcohol, or markers foralcohol.
 17. A method for portably collecting a sample from exhaledbreath of a subject, and for detecting the presence or determining thequantitative amount of at least one drug substance in said exhaledbreath, said method comprising: collecting said sample comprising atleast one of a non-volatile or volatile compound from said subject,using a system comprising a sampling unit and a housing arranged to holdsaid sampling unit, wherein said sampling unit is adapted to collect atleast one of non-volatile and volatile compounds of said at least onedrug substance from said exhaled breath from said subject, and in saidhousing comprises at least one inlet for said subject to exhale intosaid housing to said sampling unit and at least one outlet for saidexhaled breath to exit through; and analyzing said collected sampleusing mass-spectroscopy.
 18. The method according to claim 17, whereinsaid collecting comprises collecting at least one of non-volatile orvolatile compounds of said at least one drug substance from said exhaledbreath from said subject in a sampling unit held in a housing of saidsystem.
 19. The method according to claim 18, wherein said collectingcomprises said subject exhaling into at least one inlet of said housingto said sampling unit and further to at least one outlet to exit fromsaid housing.
 20. The method according to claim 17, comprisinggenerating suction by means of a pump arranged downstream said samplingunit.